condition found tbRes List
SIL, Silymarin (Milk Thistle) silibinin: Click to Expand ⟱
Features:
Silymarin (Milk Thistle) Flowering herb related to daisy and ragweed family.
Silibinin (INN), also known as silybin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds.
-a flavonoid combination of 65–80% of seven flavolignans; the most important of these include silybin, isosilybin, silychristin, isosilychristin, and silydianin. Silybin is the most abundant compound in around 50–70% in isoforms silybin A and silybin B

-Note half-life 6hrs?.
BioAv not soluble in water, low bioA (1%). 240mg yielded only 0.34ug/ml plasma level. oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL, so can on acheive levels used in most in-vitro studies.
Pathways:
- results for both inducing and reducing ROS in cancer cells. In normal cell seems to consistently lower ROS. Given low bioavailability seems unlikely one could acheieve levels in vivo to raise ROS(except level in GUT could be much higher (800uM).
- ROS↑ related: MMP↓(ΔΨm), Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑,
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, β-catenin↓, Notch2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


radioP, RadioProtective: Click to Expand ⟱
Source:
Type:
Protect against the damaging effects of radiation therapy.
Scientific Papers found: Click to Expand⟱
3306- SIL,  Rad,    Radioprotective and radiosensitizing properties of silymarin/silibinin in response to ionizing radiation
- Review, Var, NA
radioP↑, Radioprotective and radiosensitizing properties of silymarin/silibinin in response to ionizing radiation
RadioS↑, graphical abstract
TumCMig↓, mechanisms for radiosensitization of silymarin/silibinin have been reported including suppression of migration and invasion of cancer cells, inhibition of angiogenesis, induction of apoptosis and cell cycle arrest, damage to DNA
TumCI↓,
angioG↓,
Apoptosis↑,
DNAdam↓,
ROS↑, increasing the formation of free radicals, and targeting some crucial pathways.
*ROS↓, The combination of silymarin/silibinin and irradiation decreases the toxicities caused by ionizing radiation because of their antioxidant, anti-apoptotic, anti-inflammatory and other properties.
*Inflam↓,

3293- SIL,    Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer
- Review, Var, NA
hepatoP↑, Silymarin has been shown to protect the liver in both experimental models and clinical studies.
TumMeta↓, In addition to its anti-metastatic activity, silymarin has also been reported to exhibit anti-inflammatory activity
Inflam↓,
chemoP↑, The chemoprotective effects of silymarin and silibinin (its major constituent) suggest they could be applied to reduce the side effects and increase the anti-cancer effects of chemotherapy and radiotherapy in various cancer types, especially in GC
radioP↑,
Half-Life↝, silibinin showed a 6-h half-life
*GSTs↑, Oral administration of silibinin leads to an increase in glutathione S-transferase (GST) and quinone reductase (QR) activity in the liver, stomach, lungs, small bowel, and skin, in a time- and dose-dependent manner
p‑JNK↑, Silymarin significantly up-regulated the levels of phosphorylated (p)-JNK, Bax, and p-p38, and cleaved poly-ADP ribose polymerase (PARP), while it down-regulated Bcl-2 and p-ERK1/2 expression, in a dose-dependent manner.
BAX↑,
p‑p38↑,
cl‑PARP↑,
Bcl-2↓,
p‑ERK↓,
TumVol↓, Silymarin (100 mg/kg) decreased the tumor volume in an AGS xenograft mouse model and increased apoptosis in the tumors.
eff↑, resveratrol, lycopene, sulforaphane, or silybinin have been shown to have anti-tumor activity, along with relatively low-toxicity to normal cells. Therefore they could be used in combination
TumCCA↑, Silibinin induced apoptosis and cell cycle arrest in G2/M phase in MGC803 cells
STAT3↓, Silybinin down-regulated p-STAT3 protein expression and also its downstream genes (such as Mcl-1, survivin, Bcl-xL, and STAT3).
Mcl-1↓,
survivin↓,
Bcl-xL↓,
Casp3↑, Silibinin increased caspase-3 and caspase-9 mRNA and protein expression levels.
Casp9↑,
eff↑, Therefore, the anti-cancer activity of silibinin might be enhanced by HDAC inhibitors
CXCR4↓, Silymarin significantly induced apoptosis and decreased the expression level of CXCR-4 in HepG2 cells in a concentration-dependent manner.
Dose↝, It has been shown to be tolerated by patients at a large dose (700 mg) thrice per day over six months

3294- SIL,    Silymarin: a review on paving the way towards promising pharmacological agent
- Review, Nor, NA - Review, Arthritis, NA
*hepatoP↑, It improves hepatic function, lessens hepatotoxicity caused by high acetaminophen intake, and can lessen oxidative stress in experimental mice, according to a study on animals
*Inflam↓,
*chemoP↑, moreover reducing the side effect of chemotherapeutic agents.
*glucose↓, Silymarin is effective anti-diabetic as it lowers serum glucose levels thus preventing the development of diabetic nephropathy
*antiOx↑, Various studies revealed that Silymarin could exert antioxidant properties in several mechanisms, which includes direct hindrance in free radical production,
*ROS↓,
*ACC↓, down-regulation of acetyl-CoA carboxylase, fatty acid synthase, and peroxisome proliferator-activated receptor
*FASN↓,
*radioP↑, More studies have revealed radioprotective properties of Silymarin in the testis tissues of mice and rats
*NF-kB↓, Silymarin inhibits NF-kB, down-regulates TGF-ß1 mRNA
*TGF-β↓,
*AST↓, Silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of α-smooth muscle actin in fibrotic tissue
*α-SMA↝,
*eff↑, Okda et al.[Citation76] currently reported that silymarin with ginger has significantly decreased the severity and incidence of liver fibrosis.
*neuroP↑, Researchers demonstrated that silymarin inhibits microglia activation, and protects dopaminergic neurons from lipopolysaccharide (LPS)-induced neurotoxicity
eff↑, The Silymarin with a selenium dose of 570 mg/d, for 6 months caused no side effects and was effective in reducing prostate cancer growth
ROS↓, Silymarin shows anti-cancerous properties considered to be linked to oxidative stress inhibition, apoptosis induction, growth cycle arrest, and mitochondrial pathway inhibition

3297- SIL,  Rad,    Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells
- in-vitro, CRC, HCT15 - in-vitro, CRC, RKO
TumCP↓, Silymarin was found to reduce proliferation of the human colon carcinoma cells in a concentration and timedependent manner.
RadioS↑, Moreover, percentage of cell death was also increased in combined treatment (20µg/ml of silymarin + radiation)
TumCCA↑, combination increases the arrest of cells in G 2 /M phase of cell cycle, DNA damage induced decrease in MMP and a decrease of the reactive oxygen species (ROS) levels, which are associated with an increase in cell death
DNAdam↓,
MMP↓,
ROS↓,
*radioP↑, Noteworthy, since silymarin was previously shown to confer protection against radiation in at least some types of normal tissues

3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, graphical abstract
TumCCA↑,
Apoptosis↓,
TumMeta↓,
TumCG↓,
angioG↓,
chemoP↑, The chemo-protective effects of silymarin and silibinin propose that they could be applied to decrease the side effects and increase the anti-tumor effects of chemotherapy and radiotherapy in different types of cancers.
radioP↑,
p‑ERK↓, fig 2
p‑p38↓,
p‑JNK↓,
P53↑,
Bcl-2↓,
Bcl-xL↓,
TGF-β↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
Wnt↓,
Vim↓,
VEGF↓,
IL6↓,
STAT3↓,
*ROS↓,
IL1β↓,
PGE2↓,
CDK1↓, Causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9,
CycB↓,
survivin↓,
Mcl-1↓,
Casp3↑,
Casp9↑,
cMyc↓, Silibinin treatment diminishes c-MYC
COX2↓, Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, Ang-4, MMP-2, MMP-9, CCR-2 and CXCR-4
Hif1a↓,
CXCR4↓,
CSCs↓, HCT-116 cells, Induction of apoptosis, suppression of migration, elimination of CSCs. Attenuation of EMT via decreased expression of N- cadherin and vimentin and increased expression of (E-cadherin).
EMT↓,
N-cadherin↓,
PCNA↓, Decrease in PCNA and cyclin D1 level.
cycD1↓,
ROS↑, Hepatocellular carcinoma: Silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation.
eff↑, Silymarin + Curcumin
eff↑, Silibinin + Metformin
eff↑, Silibinin + 1, 25-vitamin D3
HER2/EBBR2↓, Significant down regulation of HER2 by 150 and 250 µM of silybin after 24, 48 and 72 h.

3303- SIL,    Exploring the anti-cancer and antimetastatic effect of Silymarin against lung cancer
- Review, Var, NA
chemoP↑, The chemo-protective effects of silymarin and silibinin propose that they could be applied to decrease the side effects and increase the anti-tumor effects of chemotherapy and radiotherapy in different types of cancers.
radioP↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
angioG↓,2,   Apoptosis↓,1,   Apoptosis↑,1,   BAX↑,1,   Bcl-2↓,2,   Bcl-xL↓,2,   Casp3↑,2,   Casp9↑,2,   CDK1↓,1,   chemoP↑,3,   cMyc↓,1,   COX2↓,1,   CSCs↓,1,   CXCR4↓,2,   CycB↓,1,   cycD1↓,1,   DNAdam↓,2,   Dose↝,1,   E-cadherin↑,1,   eff↑,6,   EMT↓,1,   p‑ERK↓,2,   Half-Life↝,1,   hepatoP↑,1,   HER2/EBBR2↓,1,   Hif1a↓,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,2,   p‑JNK↓,1,   p‑JNK↑,1,   Mcl-1↓,2,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   N-cadherin↓,1,   p‑p38↓,1,   p‑p38↑,1,   P53↑,1,   cl‑PARP↑,1,   PCNA↓,1,   PGE2↓,1,   radioP↑,4,   RadioS↑,2,   ROS↓,2,   ROS↑,2,   STAT3↓,2,   survivin↓,2,   TGF-β↓,1,   TumCCA↑,3,   TumCG↓,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   TumMeta↓,2,   TumVol↓,1,   VEGF↓,1,   Vim↓,1,   Wnt↓,1,  
Total Targets: 59

Results for Effect on Normal Cells:
ACC↓,1,   antiOx↑,1,   AST↓,1,   chemoP↑,1,   eff↑,1,   FASN↓,1,   glucose↓,1,   GSTs↑,1,   hepatoP↑,1,   Inflam↓,2,   neuroP↑,1,   NF-kB↓,1,   radioP↑,2,   ROS↓,3,   TGF-β↓,1,   α-SMA↝,1,  
Total Targets: 16

Scientific Paper Hit Count for: radioP, RadioProtective
6 Silymarin (Milk Thistle) silibinin
2 Radiotherapy/Radiation
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:1185  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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